Fetal tissue engineering in an ovine model

描述（由申请人提供）：在第一个项目中，我们打算改进用于创建组织工程补片的技术，该补片用于在已建立的绵羊模型中预防新生儿先天性胃肠道修复后胃肠道再疝。我们还计划研究在植入前对胎儿间充质细胞进行体外机械预处理是否会改善结局。在第二个项目中，我们将研究神经干细胞修复胎儿脊髓脊膜膨出（MMC）的神经，胃肠道和泌尿系统的结果在一个大系列的羊。在足月前约30天（妊娠110-115天），具有手术产生的MMC的胎羊将经历Gortex（TM）贴片闭合加上将神经干细胞接种到生物可降解支架上的递送。还将对适当的对照动物进行平行研究。运动、感觉和尿动力学检查将在出生后72小时内进行。将对脊髓和肛门括约肌进行组织病理学分析，以评估正常发育。在最后一个项目中，我们将描述人类和绵羊羊水间充质细胞的免疫学特性和分化潜力。

DESCRIPTION (provided by applicant): In the first project, we intend to refine the techniques for creating tissue engineered patches used to prevent gastrointestinal re-herniation after neonatal congenital diaphragmatic repair in an established ovine model. We also plan to investigate whether in vitro mechanical preconditioning of fetal mesenchymal cells prior to implantation leads to improved outcomes. In the second project, we will investigate the neurologic, gastrointestinal, and urologic outcomes of fetal myelomeningocele (MMC) repair with neural stem cells in a large series of sheep. Approximately 30 days before term (110-115 days gestation), fetal lambs with a surgically created MMC will undergo Gortex(tm) patch closure plus the delivery of neural stem cells seeded onto a biodegradable scaffold. The appropriate control animals will also be studied in parallel. Motor, sensory, and urodynamic testing will occur within 72 hours of birth. The spinal cord and anal sphincter muscles will be analyzed histopathologically to assess for normal development. In the last project, we will characterize the immunologic properties and differentiation potential of human and ovine amniotic fluid mesenchymal cells.